This proposal requests renewal of the NIEHS Center Grant "Trace Contaminants as Environmental Health Hazards to Man" for the five-year funding period 1990-1995. Now in its 15th year, this grant has provided the continuity that has been crucial to developing a national resource for the study of environmental health issues. Our overall scientific objective is to identify the mechanisms by which xenobiotics damage cells and organs and the potential hazard to human health of trace contaminants. The research is conducted through three major programs: The first exploits the Center's long-standing expertise in neurobehavioral toxicology to characterize the subtle, long-term effects of neurotoxic agents such as lead, mercury, manganese, and acrylamide and, at the same time, explores the cellular mechanisms underlying these behavioral effects. The second program focuses on pulmonary toxicology with the lung both as a portal of entry and as a target of airborne toxicants. This program builds upon forty years of continuous research at Rochester. Currently,the mechanisms of action of airborne toxicants are being investigated in specific pulmonary cell types. Cellular and molecular toxicology is the third and now largest program in the Center and plays a lead role in the application of modern techniques in biology and chemistry. This program has special expertise in receptor-mediated toxicity, oncogene expression, and bioactivation mechanisms. These programs receive scientific, technical and administrative support from six shared Center facilities: the analytical facility, biostatistics, a hazardous substance facility, laboratory animal services, pathology/morphology, and a cell and tissue culture facility. In addition, the Center's research is enriched by a visiting scientist program, pilot project awards, extramural faculty development and the Rochester International Conference Series in Environmental Toxicity. The Center contributes to and derives further enrichment from a well-established Ph.D. training program supported by an NIEHS training grant. The Center has developed many scientific collaborations involving faculty within the Medical School as well as in research institutions both at home and abroad. Thus, we are able to call upon a range of disciplines to tackle emerging problems in environmental health. The Center is also collaborating in the development of a new Occupational Health Center in the Medical School.